About 50 people were reported injured, some of them critically, Dawn News reported.
Ahmed Chinoy, head of the Citizen Police Liaison Committee, said investigators were unsure whether the blast was a terrorist act or an accident, possibly from an exploding natural gas cylinder.
The bus was parked outside the Karachi Cantonment Railway Station when it exploded with such force its roof was blown off.
The area is a hub for travel locally and to other cities in Pakistan.
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